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Background: Reserves' mechanisms explain inconsistencies between accumulation of neuropathological damage and clinical manifestations. Leisure activities are believed to promote reserves., Objective: This study evaluates whether cognitive, social, and physical leisure activities performed over life-span predict current cognitive functioning in normal aging and Alzheimer's disease (AD) continuum., Methods: 35 AD, 24 amnestic-Mild Cognitive Impairment (a-MCI) patients, 21 individuals with subjective cognitive complaint (SCD), and 25 controls underwent a questionnaire developed to quantify leisure activities in different life periods, the Addenbrooke's Cognitive Examination-Revised (ACE-R), and T1-weighted 3T-MRI scans for brain volumetrics and cortical thickness quantification. Partial/total leisure activities' scores and demographic and brain variables were entered as predictors, while ACE-R scores as dependent variables in linear regression analyses., Results: Current level of cognition was predicted by (i) social and physical activities performed in middle age and current cognitive activity in AD; (ii) cognitive and social activities performed in middle age, current age and cortical thickness in a-MCI; (iii) recreational activities the set of lifetime, current age, and brain features in SCD; (iv) education and the set of lifetime leisure activities over lifespan in controls., Conclusions: This study shows a funnel effect due to gradual reduction of stimulatory activities in the transition from healthy aging to AD. Reserve indices taking into account different types of stimulatory activities allow to capture even smallest residual effects of reserves accumulated over lifespan, until their complete depletion at advanced AD stages. These results may help target tailored interventions during normal and pathological aging., Competing Interests: Declaration of conflicting interestsL.S. and M.B. are Editorial Board Members of this journal but were not involved in the peer-review process of this article nor had access to any information regarding its peer-review. The remaining authors have no conflict of interest to report.

Cognitive training (CT) programs aim to improve cognitive performance and impede its decline. Thus, defining the characteristics of individuals who can benefit from these interventions is essential. Our objectives were to assess if the cognitive reserve (CR), APOE genotype (e4 carriers/non-carriers) and/or hippocampal volume might predict the effectiveness of a CT program. Participants were older adults without dementia (n = 226), randomized into parallel experimental and control groups. The assessment consisted of a neuropsychological protocol and additional data regarding total intracranial, gray matter, left/right hippocampus volume; APOE genotype; and Cognitive Reserve (CR). The intervention involved multifactorial CT (30 sessions, 90 min each), with an evaluation pre- and post-training (at six months); the control group simply following the center's routine activities. The primary outcome measures were the change in cognitive performance and the predictors of change. The results show that APOE-e4 non-carriers (79.1%) with a larger left hippocampal volume achieved better gains in semantic verbal fluency (R 2  = .19). Subjects with a larger CR and a greater gray matter volume better improved their processing speed (R 2  = .18). Age was correlated with the improvement in executive functions, such that older age predicts less improvement (R 2  = .07). Subjects with a larger left hippocampal volume achieved more significant gains in general cognitive performance (R 2  = .087). In conclusion, besides the program itself, the effectiveness of CT depends on age, biological factors like genotype and brain volume, and CR. Thus, to achieve better results through a CT, it is essential to consider the different characteristics of the participants, including genetic factors.Trial registration: Trial retrospectively registered on January 29th, 2020-(ClinicalTrials.gov -NCT04245579)., (© 2024. The Author(s), under exclusive licence to Marta Olivetti Belardinelli.)

Introduction : Amyotrophic lateral sclerosis (ALS) has heterogeneous manifestations ranging from motor neuron degeneration to cognitive and behavioral impairment. This study aims to clarify the interactions between cognition and behavioral symptoms with relevant disease predictors and with cognitive reserve (CR), quantified through education, physical activity, and occupation proxies. Methods : A prospective sample of 162 ALS patients and 61 controls were evaluated with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) (dependent variable), a Cognitive Reserve Index questionnaire (CRIq) and demographic data (age and sex), and, for patients, clinical variables: disease duration, site of onset, the ALS Functional Rating Scale (ALSFRS), forced vital capacity (FVC), and gene mutation chromosome 9 open reading frame 72 ( C9orf72 ) (independent variables). Multiple regression and mediation analyses were performed to predict cognitive and behavioral symptoms. Results : For the ALS group, the statistical model explained 38.8% of variance in ECAS total ( p  < 0.001), 59.4% of executive functions ( p  < 0.001), and 55% of behavioral symptoms ( p  < 0.001). For controls, it accounted for 52.8% of variance in ECAS total ( p  < 0.001). Interaction effects and mediation analysis showed CR is an ECAS total modulator, with a differential effect within groups ( p  < 0.001). Verbal fluency was the single best cognitive score to differentiate patients from controls ( p  = 0.004), and the gene mutation C9orf72 was found to be a behavioral symptom' predictor in patients ( p  = 0.009). Conclusion : This study supports the proposed concept that CR acts as a cognitive modulator in ALS patients and healthy individuals. Moreover, CR also modulates behavioral manifestations in ALS.

Introduction: The molecular basis of cognitive resilience (CR) among pathologically confirmed Alzheimer's disease (AD) cases is not well understood., Methods: Abundance of 13 cell types and neuronal subtypes in brain bulk RNA-seq data from the anterior caudate, dorsolateral prefrontal cortex (DLPFC), and posterior cingulate cortex (PCC) obtained from 434 AD cases, 318 cognitively resilient AD cases, and 188 controls in the Religious Orders Study and Rush Memory and Aging Project was estimated by deconvolution., Results: PVALB+ neuron abundance was negatively associated with cognitive status and tau pathology in the DLPFC and PCC (P adj  < 0.001) and the most reduced neuronal subtype in AD cases compared to controls in DLPFC (P adj  = 8.4 × 10 -7 ) and PCC (P adj  = 0.0015). We identified genome-wide significant association of neuron abundance with TMEM106B single nucleotide polymorphism rs13237518 in PCC (p = 6.08 × 10 -12 ). rs13237518 was also associated with amyloid beta (p = 0.0085) and tangles (p = 0.0073)., Discussion: High abundance of PVALB+ neurons may be a marker of CR. TMEM106B variants may influence CR independent of AD pathology., Highlights: Neuron retention and a lack of astrocytosis are highly predictive of Alzheimer's disease (AD) resilience. PVALB+ GABAergic and RORB+ glutamatergic neurons are associated with cognitive status. A TMEM106B single nucleotide polymorphism is related to lower AD risk, higher neuron count, and increased AD pathology., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq&#95;Working activity and specific motor cerebellar volumes: Left&#95;V (ρ = 0.40, p = 0.02), Right&#95;V (r = 0.42, p = 0.002), Vermis&#95;VIIIb (ρ = 0.47, p = 0.003), Left&#95;X (ρ = -0.46, p = 0.002) and Vermis&#95;X (r = 0.35, p = 0.03). Furthermore, CRIq&#95;Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left&#95;Crus&#95;II, Vermis VIIb, Left&#95;IX. MMSE was associated only with the Right&#95;VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left&#95;Crus&#95;I and Right&#95;Crus&#95;I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline., (© 2024. The Author(s).)

&lt;b&gt;Introduction:&lt;/b&gt; Auditory scene analysis refers to the system through which the auditory system distinguishes distinct auditory events and sources to create meaningful auditory information. The exact number of directly perceived auditory stimuli is unknown, studies suggest it may range from 3 to 5. This number differs among individuals, and potentially may indirectly indicate the ability to store and process the complex information, related to the memory load, which is combined with human cognitive processes.&lt;b&gt;Aim:&lt;/b&gt; This study aims to further identify and quantify the number of sounds that can be perceived simultaneously in a complex auditory environment.&lt;b&gt;Material and methods:&lt;/b&gt; Participants were presented with structured acoustic recordings and were asked to identify the exact number of targeted stimuli heard throughout the test. The experiment was designed to assess the auditory load and determine the maximum number of auditory stimuli that a healthy human can perceive at once.&lt;b&gt;Results:&lt;/b&gt; Our study showed that on average, participants could identify up to three sounds at once with accuracy of responses declining progressively for four sounds or more.&lt;b&gt;Conclusions:&lt;/b&gt; This study aimed to investigate the human capacity to detect and identify multiple sound signals simultaneously in a noisy environment. By understanding this ability, we sought to assess cognitive reserve in individuals. Our objective was to determine if auditory load could serve as a diagnostic tool for cognitive evaluation. We believe that further research will establish the validity of this approach, and we anticipate that it is only a matter of time before it becomes a viable method for assessing cognitive function.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a prevalent neurological disorder, but its diagnosis remains challenging. Dual-task (DT) walking performance is a reliable indicator of iNPH but less is known about the role of cognitive reserve (CR) in predicting DT walking performance., Aims: The objective of this study was to evaluate the contribution of CR on DT walking in healthy controls (HC) and in iNPH patients (iNPH-P)., Methods: 68 iNPH-P (77.2 +/- 6.7 years old) and 28 HC (74.5 +/- 5.7 years old) were evaluated on their single-task walking (Vsimple) and on 4 DT walking (walking and counting or counting backwards, naming animals, naming words beginning with the letter P) (Vcount, VcountB, Vanimals and Vletter respectively). The contribution of CR on the different DT walking speeds was compared between HC and iNPH-P. In iNPH-P, the contribution of CR on the walking speeds was compared with regard to other cognitive, functional, and socio-demographic variables., Results: Simple linear regression demonstrated a moderate influence of CR on single and DT walking speed in iNPH-P (β > 0.3, p < .001) but not in HC where the relation was not significant. In iNPH-P, results showed that CR played a major role in explaining each of the single and DT walking speeds with NPH-scale., Conclusion: As CR could be improved through the life cycle, these results support the idea of developing and supporting physical activity programs that will enrich social, physical, and cognitive resources to protect against age-related functional decline, especially in iNPH-P patients where the age-related deficits are greater., (© 2024. The Author(s).)

Background: High cognitive reserve (CR) has been related to lower dementia risk, but its association with heart disease (HD) is unknown. We aimed to explore the relation of CR to HD and cardiac structure and function., Methods and Results: Within the UK Biobank, 349 907 HD-free participants were followed up. A composite CR indicator involving education/occupation attainment/television viewing time/confiding frequency/social connection frequency/variety of leisure activities was generated, and further categorized into low/moderate/high levels. Incident HD, including coronary HD, cardiac arrhythmia, and heart failure, was ascertained on the basis of medical records. During the follow-up, a subsample (n=31 182) underwent cardiac magnetic resonance imaging to assess ventricular structure and function. Data were analyzed using Cox regression, Laplace regression, and linear regression. Compared with low CR, the hazard ratio and 95% CI of any HD for high CR was 0.78 (0.75-0.80) (including 0.68 [0.66-0.71] for coronary HD, 0.91 [0.87-0.95] for cardiac arrhythmia, and 0.63 [0.58-0.68] for heart failure). Furthermore, high CR was associated with delayed HD onset by 1.59 (95% CI, 1.37-1.82) years compared with low CR. In cardiac magnetic resonance imaging data analysis, compared with low CR, high CR was associated with larger left ventricular end-diastolic volume (β, 0.13 [95% CI, 0.09-0.17]), left ventricular end-systolic volume (β, 0.05 [95% CI, 0.01-0.10]), left ventricular stroke volume (β, 0.16 [95% CI, 0.12-0.21]), and left ventricular ejection fraction (β, 0.08 [95% CI, 0.03-0.13])., Conclusions: High CR is associated with favorable HD health. Our findings suggest that the beneficial effect of CR is not limited to dementia but also HD.

Background: Research on neurocognitive disorders and cognitive reserve in psychiatric rehabilitation patients is crucial to understanding how cognitive function impacts rehabilitation outcomes. Cognitive reserve refers to the brain's resilience to neuropathological damage, and exploring its role in psychiatric patients can provide insights into their varying responses to treatment and recovery potential. Investigating whether there are differences in cognitive reserve and neurocognitive disorders between offenders and non-offenders within psychiatric rehabilitation can help tailor interventions and improve rehabilitation strategies. This study explores cognitive reserve (CR) and neurocognitive disorders (NCDs) in a sample of psychiatric patients within a Psychiatric Rehabilitation Center, with a particular focus on differences between offenders and non-offenders following the closure of Judicial Psychiatric Hospitals in Italy (March 31, 2015)., Method: In our observational study, were recruited a total of 59 patients (20 females and 39 males, mean age = 45.39 years) from various Psychiatric Rehabilitation Communities in Southern Italy. The patients were assessed using the Structured Clinical Interview for DSM-5 (SCID-5 CV) and a battery of tests, including in particular the Cognitive Reserve Index Questionnaire (CRIq), Brief Psychiatric Rating Scale (BPRS), Aberrant Salience Inventory (ASI) and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)., Results: Results indicated significant differences between offenders and non-offenders in cognitive reserve, psychopathological symptoms and personal and social functionality., Conclusion: Understanding these distinctions is important for developing specialized therapeutic approaches that address the rehabilitation needs of each group that also include neurocognitive aspects such as cognitive reserve.

Cognitive reserve (CR) is essential in reducing natural cognitive decline. Identified in neurodegenerative pathologies, it also increasingly plays a role in the development of the symptomatic processes of numerous psychiatric pathologies. CR could help identify subgroups of elderly patients affected by primary psychosis and mood disorders and evaluate their correlation with diagnostic and therapeutic trajectories. Our observational study assessed the correlation between cognitive reserve and cognitive and psychopathological trajectories in a group of elderly inpatients in health residential centers. After two years of observation, the results indicate a correlation between cognitive reserve levels and psychopathological and cognitive trajectories. No significant variations or correlations were observed between another investigation factor, aberrant salience, and the symptoms in the above trajectories.

Objective: The present study examined the cognitive reserve (CR) theory at late stages of Alzheimer's disease (AD). The objective is to replicate previous studies and examine the complex role of education and family size as indicators of CR., Participants and Methods: This is a retrospective study included 642 patients diagnosed with AD after age 65, categorized into low education (LE, ≤ 8 years, n  = 141) and medium-high education (MHE, ≥ 9 years, n  = 442) groups. Participants were followed up longitudinally using the Mini Mental State Examination., Results: Higher education in the MHE group, but not in the LE group, correlated with delayed diagnosis. In both groups, higher education correlated with accelerated cognitive decline. In the MHE group, country of origin was associated with cognitive decline, while in the LE group, it was linked to family size., Conclusions: This study shows that in patients with MHE but not in LE, higher education resulted in delayed diagnosis. Conversely, in cases of LE, this measure may not fully reflect CR and abilities. Additionally, higher education was associated with faster deterioration, a finding that has not been replicated often in the literature. The study illustrates the complex impact of CR proxies on age of diagnosis and cognitive decline.

Cognitive functioning heterogeneity is a well-recognized phenomenon in individuals diagnosed with mood disorders. Cognitive Reserve (CR) has been linked to multiple positive outcomes, including cognitive performance in these patients. This systematic review and meta-analysis aim to provide a comprehensive analysis of the relationship between CR and cognitive functioning in individuals with mood disorders, including bipolar disorder and depressive disorders. Following PRISMA guidelines, a systematic review and meta-analysis was conducted of original research exploring the relationship between CR and cognitive performance in adult individuals with mood disorders. The literature search was conducted on PubMed, Scopus, and Web of Science, from 2002 to September 2023, and the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. Overall, 17 studies met the inclusion criteria for the systematic review and 11 for the meta-analysis. Both qualitative and quantitative findings suggested a positive relationship between CR measures and cognitive domains. CR emerges as a possible protective factor for cognitive functioning in adult individuals with mood disorders, potentially helping to mitigate the cognitive impairments associated with the disorder. These findings underscore the importance of the fact that promoting and enhancing CR could help in the cognitive prognosis of this population., Competing Interests: Declaration of competing interest SA has been a consultant to and/or has received honoraria/grants from Otsuka-Lundbeck, with no financial or other relationship relevant to the subject of this article. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, BoehringerIngelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, SanofiAventis, Sunovion, Takeda, and Viatris, outside the submitted work. IB has received honoraria and travel support from Angelini and Lundbeck and grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III supported by ERDF Funds from the European Commission (PI18/0242/PI21/0391), National Drugs Plan, and Fundación Alicia Koplowitz. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Medincell, Merck, Newron, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. The rest of authors report no biomedical financial interests or potential conflicts of interest related to the present article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We examined how brain reserve in midlife, measured by brain-predicted age difference scores (Brain-PADs), predicted executive function concurrently and longitudinally into early old age, and whether these associations were moderated by young adult cognitive reserve or APOE genotype. 508 men in the Vietnam Era Twin Study of Aging (VETSA) completed neuroimaging assessments at mean age 56 and six executive function tasks at mean ages 56, 62, and 68 years. Results indicated that greater brain reserve at age 56 was associated with better concurrent executive function (r=.10, p=.040) and less decline in executive function over 12 years (r=.34, p=.001). These associations were not moderated by cognitive reserve or APOE genotype. Twin analysis suggested associations with executive function slopes were driven by genetic influences. Our findings suggest that greater brain reserve allowed for better cognitive maintenance from middle- to old age, driven by a genetic association. The results are consistent with differential preservation of executive function based on brain reserve that is independent of young adult cognitive reserve or APOE genotype., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background:  Cognitive dysfunction is frequently seen in multiple sclerosis (MS). However, there are conflicting findings regarding the factors it is associated with., Objective:  To investigate the relationship between aerobic capacity, strength, disability, depression, fatigue, and cognitive reserve and function., Methods:  The mobile applications Trail Making Test (TMT A-B), Digit Span Test (DST), Visuospatial Memory Test (VSMT), and Tap Fast were used in the cognitive function evaluation. Functional performance was assessed with the 6-minute walk test (6MWT), 5-Time Sit-to-Sand (5STS) test, and grip strength. Cognitive Reserve Index (CRI), Beck Depression Inventory, Fatigue Severity Scale (FSS), and Nottingham Health Profile were also used., Results:  A significant difference was found between the MS and control groups only in the 6MWT, STS-5, grip strength, TMT, VSMT, and Tap Fast. Good correlation was found between the TMT-A and 6MWT and physical mobility. A fair correlation was shown between grip strength, energy, and pain status. A good correlation was found between TMT-B and 6MWT, and a fair relationship with disability, cognitive reserve, and pain. Good correlation was observed between the DST and 6MWT, left grip strength, pain, and energy status; fair correlations were found between right grip strength, cognitive reserve, and physical mobility. Good correlation was found between the VSMT and energy. A fair relationship between disability, cognitive reserve, and pain was demonstrated. Good correlation was observed between the Tap Fast score and disability, 5STS, FSS, energy, and physical mobility. A fair relationship was found between pain and social isolation., Conclusion:  It has been shown that cognitive performance in MS is related to disability, functional performance, cognitive reserve, fatigue, and general health., Trial Registration:  NCT06084182., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Background: Despite existing studies showing that physical exercise improves cognitive function in older adults either concurrently or in a delayed manner, studies examining these associations simultaneously are rare. Additionally, the underlying mechanisms in these associations remain incompletely understood., Objective: This study explores the concurrent and delayed (two years later) associations between physical exercise and older adults' cognitive function. This study also investigates the mediating roles of three negative physical, psychological, and social resources: limitations in daily abilities, depressive mood, and isolation from friends, as well as the moderating roles of cognitive reserve on these associations., Design: A cohort sample of 6646 Chinese older adults (Mean age = 69.28, SD = 7.03) is obtained from the 2016 and 2018 waves of the China Longitudinal Aging Social Survey. Regression analysis was employed to test the concurrent and delayed associations between physical exercise and cognitive function. The bootstrap method was utilized to examine the mediating roles of limitations in daily activities, depression mood, and isolation from friends. Interaction terms were generated to investigate the moderating roles of cognitive reserve., Results: Physical exercise presents concurrent and delayed positive associations with cognitive function. Limitations in daily activities, depressive mood and isolation from friends mediate the above associations. Moreover, cognitive reserve plays a significant role in buffering the concurrent and delayed negative links between depressive mood, isolation from friends, and cognitive function, with larger negative relationships observed for older adults with lower rather than higher levels of cognitive reserve., Conclusions: This study validates the concurrent and delayed benefits of physical exercise on older adults' cognitive function while elucidating the underlying mechanisms. These findings offer practical implications for health policies and intervention programs aimed at enhancing older adults' cognitive function., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited. In 1,079 older (M Age = 75.4 years; 56.0% women) LonGenity study participants without dementia at baseline and up to 12 years of annual follow-up (M follow-up = 3.9 years, SD = 2.5 years), high CR inferred from cognitive (education years), physical (number of blocks walked per day; weekly physical activity days), and social (volunteering/working; living with someone) proxies were associated with slower rates of age-related decline in global cognition - not gait speed decline. Thus, cognitive, physical, and social CR proxies are associated with cognitive decline in older adults without dementia. The multifactorial etiology and earlier decline in gait than cognition may render it less modifiable by CR proxies later in life., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A higher level of education was correlated with less severe motor impairment in Parkinson's Disease (PD). Nevertheless, there is limited evidence on the relationship between cognitive reserve and motor performance in complex situations in PD. To investigate the association between cognitive reserve and the dual-task gait effect in PD. Additionally, we examined the relationship between executive function, clinical and sociodemographic variables and, dual-task gait effects. We conducted a cross-sectional study with 44 PD participants. We evaluated dual-task effect on cadence, stride length, and gait velocity. Dual-task effects were correlated with neurophysiological factors, including cognitive reserve (Cognitive Reserve Index Questionnaire), overall cognitive performance of executive functions, a specific executive function domain (Trail Making Test), and the global cognitive status (Montreal Cognitive Assessment and Mini-Mental State Examination). Age, gender, and disease severity were considered as variables to be examined for correlation. We found that cognitive reserve did not influence gait performance under dual-task conditions in this sample. However, executive functions, age, and disease severity were associated with the dual-task effect on gait. The overall cognitive performance with respect to the Trail Making Test showed an inverse relationship in the dual-task gait effect on cadence. Our study's findings have important implications for understanding the association between executive functions, age, and disease severity with the dual-task effect on gait in PD. Pre-life factors, such as education, occupation, and leisure activity, did not contribute to coping with complex gait situations in PD., (© 2024. The Author(s).)

Background: Adverse childhood experiences (ACEs) are associated with later cognitive decline. However, the mechanisms underlying the effects of different types of ACEs are unclear. This study examined how ACEs impact cognitive function, specifically deprivation-related ACEs (DrACEs) and threat-related ACEs (TrACEs). Additionally, we explored the potential role of cognitive reserve (CR) and depression in these relationships., Methods: Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2020. CR, depressive symptoms and cognitive function measures were collected from 2020. ACEs were assessed at the 2014 Life Course Survey. The main analyses included 7113 participants aged 45 years or older. To explore potential associations, linear regression and SPSS Macro PROCESS were employed., Results: Among middle-aged and older adults, only exposure to DrACEs was associated with cognitive function ((β = -0.101 [95%CI: -0.150, -0.052]) for DrACEs = 1; (β = -0.250 [95%CI: -0.333, -0.167]) for DrACEs ≥ 2). The indirect effects mediated by CR and depressive symptoms were statistically significant., Limitations: The use of retrospective self-reported data for ACEs may introduce recall bias., Conclusions: Chinese middle-aged and older adults who have experienced DrACEs exhibit poorer cognitive function, while the association between TrACEs and cognitive function was not significant. And the impact of DrACEs on cognitive function was mediated by CR and depressive symptoms. Further research is necessary to validate our findings, establish causal links, and uncover the underlying mechanisms involved., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Subjective memory complaints (SMCs) are a memory disorder that often precedes mild cognitive impairment (MCI) or Alzheimer's disease (AD). Both individual alpha rhythms and cognitive reserve (CR) represent key features of SMCs and provide useful tools to characterize and predict the course of the disorder. We studied whether older people with SMCs may also present some abnormal resting state electroencephalogram (rsEEG) alpha rhythms, and whether alpha rhythms are associated with CR. To do this, eyes-closed rsEEG were recorded in 68 older people with and without SMCs. The individual alpha indexes alpha/theta transition frequency (TF) and individual alpha frequency peak (IAFp) were computed. TF and IAFp were also used to determine the alpha1, alpha2, and alpha3 power frequency. Results indicated no differences in TF or IAFp between older people with SMCs and controls. The SMCs group showed a reduction in alpha3 power in comparison with controls. Specifically, women with SMCs were characterized by a significant decrease in alpha3 power compared to control women. Furthermore, only in SMCs group, greater CR was associated with slow IAFp. In sum, these results suggest that TF and IAFp are two stable indexes that are not influenced by the presence of SMCs. However, the reduction in alpha3, as observed in women with SMCs, shows an abnormal posterior rsEEG at alpha power. Finally, the compensatory mechanisms of CR appear to interact with the neurophysiological mechanisms that underlie the regulation of alpha rhythms., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Asymptomatic Alzheimer's disease (AsymAD) describes the status of individuals with preserved cognition but identifiable Alzheimer's disease (AD) brain pathology (i.e., beta-amyloid (Aβ) deposits, neuritic plaques, and neurofibrillary tangles) at autopsy. In this study, we investigated the postmortem brains of a cohort of AsymAD subjects to gain insight into the mechanisms underlying resilience to AD pathology and cognitive decline. Our results showed that AsymAD cases exhibit enrichment in core plaques, decreased filamentous plaque accumulation, and increased plaque-surrounding microglia. Less pathological tau aggregation in dystrophic neurites was found in AsymAD brains than in AD brains, and tau seeding activity was comparable to that in healthy brains. We used spatial transcriptomics to characterize the plaque niche further and revealed autophagy, endocytosis, and phagocytosis as the pathways associated with the genes upregulated in the AsymAD plaque niche. Furthermore, the levels of ARP2 and CAP1, which are actin-based motility proteins that participate in the dynamics of actin filaments to allow cell motility, were increased in the microglia surrounding amyloid plaques in AsymAD cases. Our findings suggest that the amyloid-plaque microenvironment in AsymAD cases is characterized by the presence of microglia with highly efficient actin-based cell motility mechanisms and decreased tau seeding compared with that in AD brains. These two mechanisms can potentially protect against the toxic cascade initiated by Aβ, preserving brain health, and slowing AD pathology progression., (© 2024. The Author(s).)

Objective: Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative condition featuring variable degrees of motor and cognitive impairment. We assessed the impact of specific, empirically derived occupational skills and requirements on cognitive and motor functioning in ALS., Methods: Individuals with ALS (n = 150) were recruited from the University of Pennsylvania's Comprehensive ALS Clinic. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) measured cognition, and the Penn Upper Motor Neuron (PUMNS) and ALS Functional Rating Scales (ALSFRS-R) measured motor symptoms. We derived 17 factors representing distinct occupational skills and requirements from the Occupational Information Network (O*NET), which were related to cognitive and motor scores using multiple linear regression., Results: Occupational roles involving greater reasoning ability (β = 2.12, p  < .05), social ability (β = 1.73, p  < .05), analytic skills, (β = 3.12, p  < .01) and humanities knowledge (β = 1.83, p <.01) were associated with better performance on the ECAS, while jobs involving more exposure to environmental hazards (β=-2.57, p  < .01) and technical skills (β=-2.16, p <.01) were associated with lower ECAS scores. Jobs requiring more precision skills (β = 1.91, p  < .05) were associated with greater motor dysfunction on the PUMNS., Conclusions: Occupational histories involving more cognitively complex skills and activities were related to preserved cognitive functioning in ALS consistent with the cognitive reserve hypothesis, while jobs with greater exposure to environmental hazards and technical demands were linked to poorer cognitive functioning. Jobs involving more repetitive movements were associated with worse motor functioning, possibly due to overuse. Occupational history provides insight into protective and risk factors for variable degrees of cognitive and motor dysfunction in ALS.

Introduction: The present study aimed to explore the suitability of the vocabulary knowledge (VOC) test as an accurate and reliable proxy of cognitive reserve (CR) by evaluating its psychometric properties and discrimination accuracy compared with other CR measures in multiple sclerosis (MS)., Methods: Sixty-eight consecutive people with multiple sclerosis (pwMS), followed at our MS outpatient clinic, completed a clinical evaluation and neuropsychological assessment including: VOC, Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Cognitive Reserve Index Questionnaire (CRIq), Beck Depression Inventory-II, and State-Trait Anxiety Inventory. Reliability, convergent and divergent validity, and discrimination accuracy of the VOC were assessed using educational level as reference standard. The possible effects of sociodemographic and clinical factors on VOC and their role in predicting global cognitive status were also explored., Results: VOC demonstrated good internal consistency (Cronbach's α = 0.894) and adequate construct validity. It showed an acceptable level of discrimination between pwMS with high and low CR, comparable to the CRIq score. Education strongly affected VOC scores, which in turn were independent of MS features. VOC emerged as an independent predictor of global cognitive status together with MS-related disability., Conclusion: We demonstrated the validity of VOC as a reliable CR measure in pwMS. Thus, CR may also be estimated using fixed objective measures, independent of brain pathology and clinical features. Early CR estimation may help clinicians identify pwMS at a higher risk of cognitive decline and plan strict neuropsychological monitoring and cognitive interventions., (© 2024. The Author(s).)

Emotional intelligence (EI) and neurocognition (NC) impairments are common in first-episode psychosis (FEP), yet their evolution over time remains unclear. This study identified patient profiles in EI and NC performance in FEP. 98 adult FEP patients and 128 healthy controls (HCs) were tested on clinical, functional, EI, and NC variables at baseline and two-year follow-up (FUP). A repeated-measures ANOVA compared the effects of group (patients and HCs) and time on EI. Significant EI improvements were observed in both groups. Four groups were created based on NC and EI performance at baseline and FUP in patients: impairment in NC and EI, impairment in NC only, impairment in EI only, and no impairment. At FUP, patients impaired in NC and EI showed less cognitive reserve (CR), greater negative and positive symptoms, and poorer functional outcomes. At FUP, three group trajectories were identified: (I) maintain dual impairment (II) maintain no impairment or improve, (III) maintain sole impairment or worsen. The maintain dual impairment group had the lowest levels of CR. EI and NC impairments progress differently in FEP. Greater CR may protect against comorbid EI/NC impairment. Identifying these patient characteristics could contribute to the development of personalised interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Janssen, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work.A. Tortorella received research support and travel grants from Lundbeck and Angelini (unrelated to the present work). G. Menculini received travel grants from Angelini and Janssen. J.A. Ramos-Quiroga was on the speakers’ bureau and/or acted as consultant for Eli-Lilly, Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogui, Lundbeck, Almirall, Braingaze, Sincrolab, Medice and Rubió, Raffo in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogui, Bial, Medice and Eli- Lilly. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 5 years: Eli-Lilly, Lundbeck, Janssen- Cilag, Actelion, Shire, Ferrer, Oryzon, Roche, Psious, and Rubió. M. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda A. Gonzalez-Pinto has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Alter, Angelini, Novartis, Rovi, Takeda, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), the Basque Government, and the European Framework Program of Research. V. Balanzá-Martínez has received honoraria from Angelini, unrelated to the present work. Dr. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received grants from: Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/ BMD-2422 AGES; S2017/BMD-3740), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Casen-Recordati, Angelini, Rovi. S. Salmeron has received medical education and training courses support from rovi, rubio, Janseen-Cilag, and Casen Recordati and travel support from Rovi. A. Roldán has served as advisor or speaker for the companies Otsuka and Angelini (unrelated to the present work). P. A. Sáiz has been a consultant to and/or has received honoraria or grants from Adamed, Alter, CIBERSAM, Ethypharm Digital Therapy, European Commission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas and Servier. I. Baeza has received honoraria and travel support from Angelini, Otsuka-Lundbeck and Janssen, grants from Spanish Ministry of Health, ISCIII (FIS18/0242/FIS21/0391), co-financed by the European Union, National Drugs Plan (2022I053) and Alicia Koplowitz Foundation. The rest of authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Aging primarily affects memory and executive functions, a relationship that may be underpinned by the fact that almost all adults over 60 years old develop small vessel disease (SVD). The fact that a wide range of neuropathologies could only explain up to 43% of the variation in age-related cognitive impairment suggests that other factors, such as cognitive reserve, may play a role in the brain's resilience against aging-related cognitive decline. This study aims to examine the relationship between structural-functional-connectivity coupling (SFC), and aging, cognitive abilities and reserve, and SVD-related neuropathologies using a cohort of n = 176 healthy elders from the Harvard Aging Brain Study. The SFC is a recently proposed biomarker that reflects the extent to which anatomical brain connections can predict coordinated neural activity. After controlling for the effect of age, sex, and years of education, global SFC, as well as the intra-network SFC of the dorsolateral somatomotor and dorsal attention networks, and the inter-network SFC between dorsolateral somatomotor and frontoparietal networks decreased with age. The global SFC decreased with total cognitive score. There were significant interaction effects between years of education versus white matter hyperintensities and between years of education versus cerebral microbleeds on inter-network SFC. Enlarged perivascular space in basal ganglia was associated with higher inter-network SFC. Our results suggest that cognitive ability is associated with brain coupling at the global level and cognitive reserve with brain coupling at the inter-functional-brain-cluster level with interaction effect from white matter hyperintensities and cerebral microbleed in a cohort of healthy elderlies., (© 2024. The Author(s).)

We tested if cognitive and brain reserve and maintenance explain individual differences in episodic memory and other cognitive domains from late middle to early older adulthood. We used The Vietnam Era Twin Study of Aging data (n=1604 men) with episodic memory measured at mean ages of 56, 62 and 68 years, and magnetic resonance imaging data for a subsample of participants (n=321). Cognitive reserve -young adult general cognitive ability at a mean age of 20 years and, to a lesser degree, educational attainment- was positively related to episodic memory performance at each assessment, but not to memory change. We found no evidence for the associations of brain reserve or brain maintenance on memory change. Results were highly similar when looking at processing speed, executive function and verbal fluency. In conclusion, higher young adult cognitive reserve was related to better episodic memory in midlife and older adulthood, but it did not confer better cognitive maintenance with respect to memory. This supports the importance of early cognitive development in dementia prevention., Competing Interests: Declaration of Competing Interest The authors have no actual or potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cognitive reserve (CR) is considered a protective factor for cognitive function and may explain interindividual differences of cognitive performance given similar levels of neurodegeneration, e.g., in Alzheimer´s disease. Recent evidence suggests that CR is also relevant in Parkinson's disease (PD)., Objective: We aimed to explore the role of life-stage specific CR for overall cognition and specific cognitive domains cross-sectionally and longitudinally in PD., Methods: The cross-sectional analysis with data from the DEMPARK/LANDSCAPE study included 81 individuals without cognitive impairment (PD-N) and 87 individuals with mild cognitive impairment (PD-MCI). Longitudinal data covered 4 years with over 500 observations. CR was operationalized with the Lifetime of Experiences Questionnaire (LEQ), capturing the complexity of lifestyle activities across distinct life-stages. Cognition was assessed using a comprehensive neuropsychological test battery., Results: Higher LEQ scores, particularly from mid- and late-life, were observed in PD-N compared to PD-MCI [F(1,153) = 4.609, p = .033, η p 2  = 0.029]. They were significantly associated with better cognitive performance (0.200 ≤ β ≤ 0.292). Longitudinally, linear mixed effect models (0.236 ≤ marginal R 2  ≤ 0.441) revealed that LEQ scores were positively related to cognitive performance independent of time. However, the decline in overall cognition and memory over time was slightly more pronounced with higher LEQ scores., Conclusions: This study emphasizes the association between complex lifestyle activities and cognition in PD. Data indicate that while CR might be related to a delay of cognitive decline, individuals with high CR may experience a more pronounced drop in overall cognition and memory. Future studies will have to replicate these findings, particularly regarding domain-specific effects and considering reverse causal mechanisms., (© 2024. The Author(s).)

Background: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to a higher risk of dementia. We examined whether high levels of cognitive reserve (CR) can attenuate the increased dementia risk and brain pathologies associated with CMDs., Methods: Within the UK Biobank, 216,178 dementia-free participants aged ≥ 60 were followed for up to 15 years. Baseline CMDs and incident dementia were ascertained from medical records, medication use, and medical history. Latent class analysis was used to generate an indicator of CR (low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain MRI scans during follow-up. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, as well as mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts., Results: At baseline, 43,402 (20.1%) participants had at least one CMD. Over a mean follow-up of 11.7 years, 6,600 (3.1%) developed dementia. The presence of CMDs was associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, the HRs of dementia for people with CMDs and moderate-to-high CR and low CR were 1.78 [1.66, 1.91] and 2.13 [1.97, 2.30]), respectively (reference: CMD-free, moderate-to-high CR). Dementia risk was 17% lower (HR 0.83 [0.77, 0.91], p < 0.001) among people with CMDs and moderate-to-high compared to low CR. On brain MRI, CMDs were associated with smaller GMV (β -0.18 [-0.22, -0.13]) and HV (β -0.13 [-0.18, -0.08]) as well as significantly larger WMHV (β 0.06 [0.02, 0.11]) and MD (β 0.08 [0.02, 0.13]). People with CMDs and moderate-to-high compared to low CR had significantly larger GMV and HV, but no differences in WMHV, MD, or FA., Conclusions: Among people with CMDs, having a higher level of CR was associated with lower dementia risk and larger gray matter and hippocampal volumes. The results highlight a mentally and socially active life as a modifiable factor that may support cognitive and brain health among people with CMDs., (© 2024. The Author(s).)

Background: Leveraging Alzheimer's disease (AD) imaging biomarkers and longitudinal cognitive data may allow us to establish evidence of cognitive resilience (CR) to AD pathology in-vivo. Here, we applied latent class mixture modeling, adjusting for sex, baseline age, and neuroimaging biomarkers of amyloid, tau and neurodegeneration, to a sample of cognitively unimpaired older adults to identify longitudinal trajectories of CR., Methods: We identified 200 Harvard Aging Brain Study (HABS) participants (mean age = 71.89 years, SD = 9.41 years, 59% women) who were cognitively unimpaired at baseline with 2 or more timepoints of cognitive assessment following a single amyloid-PET, tau-PET and structural MRI. We examined latent class mixture models with longitudinal cognition as the dependent variable and time from baseline, baseline age, sex, neocortical Aβ, entorhinal tau, and adjusted hippocampal volume as independent variables. We then examined group differences in CR-related factors across the identified subgroups from a favored model. Finally, we applied our favored model to a dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 160, mean age = 73.9 years, SD = 7.6 years, 60% women)., Results: The favored model identified 3 latent subgroups, which we labelled as Normal (71% of HABS sample), Resilient (22.5%) and Declining (6.5%) subgroups. The Resilient subgroup exhibited higher baseline cognitive performance and a stable cognitive slope. They were differentiated from other groups by higher levels of verbal intelligence and past cognitive activity. In ADNI, this model identified a larger Normal subgroup (88.1%), a smaller Resilient subgroup (6.3%) and a Declining group (5.6%) with a lower cognitive baseline., Conclusion: These findings demonstrate the value of data-driven approaches to identify longitudinal CR groups in preclinical AD. With such an approach, we identified a CR subgroup who reflected expected characteristics based on previous literature, higher levels of verbal intelligence and past cognitive activity., (© 2024. The Author(s).)

Cognitive Reserve (CR) reflects acquired knowledge, skills, and abilities throughout life, and it is known for modulating cognitive efficiency in healthy and clinical populations. CR, which was initially proposed to explain individual differences in the clinical presentation of dementia, has subsequently been extended to healthy ageing, showing its role in cognitive efficiency also during middle age. Recently, CR has been linked to affective processes in psychiatric conditions such as schizophrenia, major depressive and anxiety symptoms, and psychological distress, suggesting its potential role in emotional expression and regulation. Whether the role of CR in mental health extends to non-pathological adults, and whether this is only relevant in older age is not yet clear. The aim of this work was therefore to explore the relationship between CR and mental health in healthy adults, with a focus on middle adulthood (40-60). In a sample of 96 participants, we found a positive association between CR and mental health outcomes, such that a higher cognitive reserve index corresponded to fewer mental health reported symptoms. Specifically, a higher CR reflecting professional activities was associated with lower stress levels, especially in middle agers. Taken together, these data therefore suggest that engaging occupations may help maintain a robust mental health, especially by reducing stress symptoms during middle age. These results broaden previous findings suggesting that CR relates to affective components of mental health in middle aged and older adults., (© 2024. The Author(s).)

Introduction: The proxies used to compose cognitive reserve (CR) for patients of a first episode of psychosis (FEP) have varied in the literature. The development of FEP is linked to peripheral pathways of the central nervous system, yet despite this knowledge, no research has considered the introduction of biomarkers as proxies for CR. Meanwhile, schizophrenia has been linked to the metabolic system, indicating that alterations in the levels of biological parameters, in particular high-density lipoproteins (HDL), cause worse global functioning and cognitive impairment. For these reasons, the present study aimed to create a quantifiable and objective CR index that adjusts for the multifactorial nature of FEP., Materials and Methods: We included 668 FEP patients and 217 healthy controls. Participants were assessed for sociodemographic information, years of education, employment status, premorbid IQ and biological parameters: waist circumference, hypertension, and levels of HDL, triglycerides, and glucose., Results: The findings suggest that the years of education proxy showed correlational and higher relationship with HDL levels for both FEP patients (r=0.23, b=0.185) and controls (r=0.31, b=0.342). We found that the CR index composed of years of education and HDL levels showed a higher explanatory power for the phenomenon than the classical CR index composed of years of education, employment status and premorbid IQ., Conclusions: This article proposes an objective and quantifiable method to measure CR that is more the multifactorial nature of FEP., (Copyright © 2023 SEP y SEPB. Published by Elsevier España S.L.U. All rights reserved.)

Introduction: Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ)., Material and Methods: A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny., Results: Patients with SCZ showed lower CR than those in the ESP (p<0.001). CR correctly classified 79.6% of the cases (p<0.001; Exp(B)=1.062). In ESP group, CR was related to working memory (p=0.030) and negative symptoms (p=0.027). CR (t=3.925, p<0.001) and cannabis use (t=2.023, p=0.048) explained 26.7% of the variance on functioning (p=0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R 2 =0.091, p=0.001) and functioning (R 2 =0.074, p=0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p=0.037) was mediated by CR level (p=0.003)., Conclusions: The implications of CR depend on the stage of the disease (ESP vs. SCZ), with a greater effect on neurocognition and negative symptoms in patients with chronic SCZ., (Copyright © 2024 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)

Background: Cognitive reserve (CR) involves an individual's ability to maintain cognitive vitality over their lifespan. Glucocerebrosidase (GBA) gene mutations contribute to additional effects on cognitive function in Parkinson's disease (PD) patients, but the interplay between GBA mutations and CR remains unclear. We investigated the interactions among CR, GBA, and diseases, aiming to examine whether the CR established at different stages interacts with specific genotypes to affect cognitive function., Methods: Three hundred and eighteen participants' CR indicators (i.e., education, occupation, and social function) and comprehensive neuropsychological function (i.e., tests for executive function, attention/working memory, visuospatial function, memory, and language) were evaluated., Results: We found that CR established in a specific life stage influences the individual's cognitive function, particularly in PD, based on their distinct GBA rs9628662 genotypes. Attention/working memory and memory performance are affected by occupational complexity in midlife in PD patients with the GG genotype (q < 0.0001; q < 0.0001) and healthy adults with the T genotype (q = 0.0440; q < 0.0001). Language is influenced by early education and occupation, and the effects of occupation are also observed in PD patients with the GG genotype (q = 0.0040) and in healthy adults carrying the T genotype (q = 0.0040)., Conclusions: CR, established at different life stages, can be influenced by the GBA rs9628662 genotype, impacting later-life cognition. Validating genotypes and incorporating genotype information when assessing cognitive reserve effects is crucial and can enhance targeted cognitive training., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Older adult executive function varies widely due to brain and cognitive aging. Variance in older adult executive function is linked to increased response conflict from cognitive and brain aging. Cognitive reserve (CR) is a theoretical protective mechanism that lessens brain aging's impact on cognition and is associated with greater educational attainment. Recent work in rest-state functional magnetic resonance imaging (fMRI) suggests CR proxies moderate the relationship between functional connectivity (FC) and cognitive performance. Brain network FC in "control networks," including the salience (SN), dorsal attention and frontoparietal networks, are associated with cognitive processes in older adults. CR is hypothesized to maintain cognitive processing in part through changes in how brain networks respond to cognitive demands. However, it is unclear how CR proxies like educational attainment are related to control network FC during performance when cognitive demands are increased relative to rest. Because CR is expressed more in those with higher education, we hypothesized stronger control network FC would relate to better performance, where this relationship would be strongest among the most educated., Methods: We collected flanker task data during fMRI to assess the impact of a CR proxy (i.e., educational attainment) on response conflict among older adult subjects (n = 42, age = 65-80)., Results: Linear mixed-effects models showed more educated older adults with greater SN-FC had a smaller flanker effect (i.e., less influence of distractors; p < .001) during task performance., Discussion: For the first time, we show that educational attainment moderates the relationship between task-state SN-FC and executive function among older adults., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Introduction: We investigated the association of cognitive reserve (CR) with transitions across cognitive states and death., Methods: This population-based cohort study included 2631 participants (age ≥60 years) who were dementia-free at baseline and regularly examined up to 15 years. Data were analyzed using the Markov multistate models., Results: Each 1-point increase in the composite CR score (range: -4.25 to 3.46) was significantly associated with lower risks of transition from normal cognition to cognitive impairment, no dementia (CIND) (multivariable-adjusted hazards ratio = 0.78; 95% confidence interval = 0.72-0.85) and death (0.85; 0.79-0.93), and from CIND to death (0.82; 0.73-0.91), but not from CIND to normal cognition or dementia. A greater composite CR score was associated with a lower risk of transition from CIND to death in people aged 60-72 but not in those aged ≥ 78 years., Discussion: CR contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia., Highlights: We use Markov multistate model to examine the association between cognitive reserve and transitions across cognitive states and death. A great cognitive reserve contributes to cognitive health by delaying cognitive deterioration in the prodromal phase of dementia. A great cognitive reserve is associated with a lower risk of transition from cognitive impairment, no dementia to death in people at the early stage of old age, but not in those at the late stage of old age., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The locus coeruleus-noradrenaline system regulates brain-wide neural activity involved in cognition and behavior. Integrity of this subcortical neuromodulatory system is proposed to be a substrate of cognitive reserve that may be strengthened by lifetime cognitive and social activity. Conversely, accumulation of tau tangles in the brainstem locus coeruleus nuclei is recently studied as a very early marker of Alzheimer's disease (AD) pathogenesis and cognitive vulnerability, even among older adults without cognitive impairment or significant cerebral AD pathologies. This clinical-pathologic study examined whether locus coeruleus tangle density was cross-sectionally associated with lower antemortem cognitive performance and social activity among 142 cognitively unimpaired and impaired older adults and whether social activity, a putative reserve factor, mediated the association of tangle density and cognition. We found that greater locus coeruleus tangle density was associated with lower social activity for the whole sample and in the cognitively unimpaired group alone and these associations were independent of age, sex, education, depressive symptoms, and burden of cerebral amyloid and tau. The association of locus coeruleus tangle density with lower cognitive performance was partially mediated by level of social activity. These findings implicate the locus coeruleus-noradrenaline system in late-life social function and support that locus coeruleus tangle pathology is associated with lower levels of social activity, independent of cerebral AD pathologies, and specifically among older adults who are cognitively unimpaired. Early brainstem pathology may impact social function, and level of social function, in turn, influences cognition, prior to canonical stages of AD., (© 2024. The Author(s).)

Introduction: Cognitive reserve might mitigate the risk of Alzheimer's dementia among memory clinic patients. No study has examined the potential modifying role of stress on this relation., Methods: We examined cross-sectional associations of the cognitive reserve index (CRI; education, occupational complexity, physical and leisure activities, and social health) with cognitive performance and AD-related biomarkers among 113 memory clinic patients. The longitudinal association between CRI and cognition over a 3-year follow-up was assessed. We examined whether associations were influenced by perceived stress and five measures of diurnal salivary cortisol., Results: Higher CRI scores were associated with better cognition. Adjusting for cortisol measures reduced the beneficial association of CRI on cognition. A higher CRI score was associated with better working memory in individuals with higher (favorable) cortisol AM/PM ratio, but not among individuals with low cortisol AM/PM ratio. No association was found between CRI and AD-related biomarkers., Discussion: Physiological stress reduces the neurocognitive benefits of cognitive reserve among memory clinic patients., Highlights: Physiological stress may reduce the neurocognitive benefits accrued from cognitively stimulating and enriching life experiences (cognitive reserve [CR]) in memory clinic patients. Cortisol awakening response modified the relation between CR and P-tau 181 , a marker of Alzheimer's disease (AD). Effective stress management techniques for AD and related dementia prevention are warranted., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The prevalence of neurodegenerative disorders, particularly dementia, is on the rise across many countries worldwide. This negative trend calls for improving our understanding of cognitive aging. While motor-cognitive dual-task approaches have already been proven valuable for clinical diagnosis, comparatively less research is available on the application of Cognitive-Cognitive Dual-Tasking (CCDT), across several cognitive domains. Moreover, there is limited understanding about how healthy aging affects performance in such dual-tasks in the general population. CCDT entails engaging individuals in multiple cognitive tasks simultaneously and holds promise for remote e-Health interventions. In this cross-sectional study, our objective was to evaluate the suitability of a newly developed, self-administered, online tool for examining age-related differences in memory performance under dual-tasking. 337 healthy adults aged 50-90 underwent a visual memory test (Memo) under both single and dual-task conditions (attend to auditory letters). Additional measures included questionnaires on subjective memory complaints (MAC-Q), on cognitive reserve (CR), and a cognitive screening (auto-GEMS). As expected, the accuracy of visual memory performance exhibited a negative correlation with age and MAC-Q, and a positive correlation with CR and auto-GEMS scores. Dual-tasking significantly impaired performance, and its detrimental effect decreased with increasing age. Furthermore, the protective effect of cognitive reserve diminished with advancing age. These findings suggest that the commonly observed age-related increase in dual-task costs is not universally applicable across all tasks and cognitive domains. With further refinement, a longitudinal implementation of this approach may assist in identifying individuals with a distinct cognitive trajectory and potentially at a higher risk of developing cognitive decline., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Contemori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Mild cognitive impairment (MCI) describes an aging profile characterized by a cognitive decline that is worse than expected in normal aging but less pervasive and critical than full-blown dementia. In the absence of an effective treatment strategy, it is important to identify factors that can protect against progression to dementia. In this field, it is hypothesized that one aspect that may be a protective factor against the neurotypical outcome of dementia is cognitive reserve (CR). Cognitive reserve is the ability to maintain cognitive functionality despite accumulating brain pathology., Objectives: The present study aimed to identify and analyze the differences in CR between healthy adults and patients with MCI. Specifically, it is hypothesized that (i) healthy older adult people have higher CR than older adult people diagnosed with MCI, and (II) CR could predict the classification of subjects into people with or without MCI., Methods: Two hundred forty-three adults (mean age = 60.4, SD = 7.4) participated in the present study and were classified into three groups based on Petersen's MCI criteria: healthy controls (HC), amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The Cognitive Reserve Index questionnaire (CRIq) was administered to assess the level of CR, FINDINGS: Results showed that HC had significantly higher CR scores than participants diagnosed with aMCI and naMCI. Moreover, a binomial logistic regression suggested that low CR was a significant risk factor for the MCI diagnosis., Conclusions: The clinical picture that emerged from the results showed that lower CR could be considered a characteristic of pathological aging, such as MCI.Public significance statement, Since the brain attempts to cope with life-related changes or pathologies, it is fundamental for both clinicians and researchers to investigate further the factors that contribute to brain resilience. As an indirect expression of brain reserve, cognitive reserve may be both a marker and a predictor of adaptive aging., (© 2024. The Author(s).)

Objective: Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied., Methods: We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing., Results: Overall, mTBI OA performed worse than healthy OA ( p  = 0.031). Lower CR generally decreased performance ( p  < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR ( p  = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA ( p  = 0.05). There was no clear effect of CR on P2 or P3 measures., Conclusion: As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Background: Cognitive reserve (CR) has been linked to dementia, yet its influence on the risk of depression and related outcomes remains unknown. We aimed to examine the association of CR with depression and subsequent dementia or death, and to assess the extent to which CR is related to depression-free survival., Methods: Within the UK Biobank, 436,232 participants free of depression and dementia were followed. A comprehensive CR indicator (low, moderate, and high) was created using latent class analysis based on information on education, occupation, mentally passive sedentary behavior, social connection, confiding with others, and leisure activities. Depression, dementia, and survival status were ascertained through self-reported medical history and/or linkages to medical records. Data were analyzed using multi-state Markov model and Laplace regression., Results: Over a median follow-up of 12.96 years, 16,560 individuals developed depression (including 617 with subsequent dementia) and 28,655 died. In multivariable multi-state models, compared with low CR, high CR was associated with lower risk of depression (hazard ratio 0.53 [95% confidence interval 0.51-0.56]) and lower risk of post-depression dementia (0.55 [0.34-0.88]) or death (0.69 [0.55-0.88]) in middle-aged adults (aged <60 years). In Laplace regression, the depression-free survival time was prolonged by 2.77 (2.58-2.96) years in participants with high compared to low CR., Conclusions: High CR is associated with lower risks of depression and subsequent transitions to dementia and death, particularly in middle age. High CR may prolong depression-free survival. Our findings highlight the importance of enhancing CR in the prevention and prognosis of depression.

With dementia incidence projected to escalate significantly within the next 25 years, the United Nations declared 2021-2030 the Decade of Healthy Ageing, emphasising cognition as a crucial element. As a leading discipline in cognition and ageing research, psychology is well-equipped to offer insights for translational research, clinical practice, and policy-making. In this comprehensive review, we discuss the current state of knowledge on age-related changes in cognition and psychological health. We discuss cognitive changes during ageing, including (a) heterogeneity in the rate, trajectory, and characteristics of decline experienced by older adults, (b) the role of cognitive reserve in age-related cognitive decline, and (c) the potential for cognitive training to slow this decline. We also examine ageing and cognition through multiple theoretical perspectives. We highlight critical unresolved issues, such as the disparate implications of subjective versus objective measures of cognitive decline and the insufficient evaluation of cognitive training programs. We suggest future research directions, and emphasise interdisciplinary collaboration to create a more comprehensive understanding of the factors that modulate cognitive ageing., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study we investigated the relationship between cognitive reserve (CR) proxies, such as education, physical activity (PA), and cognitive dysfunction (CD) in the presence or absence of frontotemporal disorders (FTD). Previous research has suggested that education and PA may delay the onset of CD and reduce the risk of developing dementia. However, it remains unclear whether these CR proxies can protect against CD when FTD is present. We aimed to explore this relationship and determine whether sustained CR may be evident regardless of FTD. We recruited 149 older adults (aged 65-99 years) from community centers where they were voluntarily participating in leisure activities. We used bioelectrical impedance to measure their body composition, and we administered the International PA Questionnaire and the Mini-Mental State Examination to measure their PA and cognitive function, respectively. We used the Frontal Assessment Battery to screen for frontotemporal dementia. Our results showed that people with FTD were older, had lower education, and engaged in less PA, relative to other participants. Regression models revealed that age, education, and PA were significant predictors of FTD. More specifically, FTD was negatively associated with cognitive functioning, and there were significant interaction effects between FTD and education and PA. PA and education were significant predictors of cognitive functioning, and, when values for PA and education were high, they offset the effects of FTD on cognitive function. These findings support impressions that PA and years of education provide an insulating or compensatory effect on cognitive functioning in older adults with executive dysfunction or frontotemporal dementia, highlighting the importance of encouraging both pursuits., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cognitive reserve explains the differences in the susceptibility to cognitive impairment related to brain aging, pathology, or insult. Given that cognitive reserve has important implications for the cognitive health of typically and pathologically aging older adults, research needs to identify valid and reliable instruments for measuring cognitive reserve. However, the measurement properties of current cognitive reserve instruments used in older adults have not been evaluated according to the most up-to-date COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN). This systematic review aimed to critically appraise, compare, and summarize the quality of the measurement properties of all existing cognitive reserve instruments for older adults. A systematic literature search was performed to identify relevant studies published up to December 2021, which was conducted by three of four researchers using 13 electronic databases and snowballing method. The COSMIN was used to assess the methodological quality of the studies and the quality of measurement properties. Out of the 11,338 retrieved studies, only seven studies that concerned five instruments were eventually included. The methodological quality of one-fourth of the included studies was doubtful and three-seventh was very good, while only four measurement properties from two instruments were supported by high-quality evidence. Overall, current studies and evidence for selecting cognitive reserve instruments suitable for older adults were insufficient. All included instruments have the potential to be recommended, while none of the identified cognitive reserve instruments for older adults appears to be generally superior to the others. Therefore, further studies are recommended to validate the measurement properties of existing cognitive reserve instruments for older adults, especially the content validity as guided by COSMIN.Systematic Review Registration numbers: CRD42022309399 (PROSPERO)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The effects of sleep-wake behavior on perceived fatigability and cognitive abilities when performing daily activities have not been investigated across levels of cognitive reserve (CR)., Methods: CR Index Questionnaire (CRIq) data were collected and subjected to moderated mediation analysis., Results: In amnestic mild cognitive impairment (aMCI; n = 41), CR moderated sleep-related impairments (SRIs), and fatigability at low CR (CRIq < 105.8, p = 0.004) and mean CR (CRIq = 126.9, p = 0.03) but not high CR (CRIq > 145.9, p = 0.65) levels. SRI affected cognitive abilities mediated by fatigability at low CR (p < 0.001) and mean CR (p = 0.003) levels. In healthy controls (n = 13), SRI in fatigability did not alter cognitive abilities across CR levels; controls had higher leisure scores than patients with aMCI (p = 0.003, effect size = 0.93)., Discussion: SRI can amplify impaired cognitive abilities through exacerbation of fatigability in patients with aMCI with below-mean CR. Therefore, improving sleep-wake regulation and leisure activities may protect against fatigability and cognitive decline., Highlights: Clinical fatigue and fatigability cannot be alleviated by rest. Clinical fatigability disrupts daily activities during preclinical Alzheimer's. High cognitive reserve mitigates sleep-wake disturbance effects. High cognitive reserve attenuates clinical fatigability effects on daily functioning. Untreated obstructive sleep apnea potentiates Alzheimer's pathology in the brain., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Cognition is a mental process that provides the ability to think, know, and learn. Though cognitive skills are necessary to do daily tasks and activities, cognitive aging causes changes in various cognitive functions. Cognitive abilities that are preserved and strengthened by experience can be kept as a reserve and utilized when necessary. The concept of reserving cognition was found when people with Alzheimer's disease had differences in clinical manifestations and cognitive functions. The cognitive reserve builds resilience against cognitive decline and improves the quality of life. Also, several lines of studies have found that the plasticity between neurons has a significant impact on cognitive reserve and acts against cognitive decline. To extend the findings, the present study provides a comprehensive understanding of cognitive reserve and the variables that are involved in maintaining cognition. The study also considers reading as one of the cognitive proxies that develops and maintains cognitive reserve., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A common belief among people and some researchers is that keeping yourself mentally active may decrease the risk of dementia. Over the past years, despite widespread efforts to identify proxies for protecting cognitive reserve against age-related changes, it is still not clear what type of intellectual activity would be beneficial for cognitive reserve. To fill this gap, we propose a three-dimensional model of intellectual activity. According to this conceptual model, intellectual activities could be distinguished based on their locations in a three-dimensions space, including; (1) Activation: active vs. passive, (2) Novelty: novel vs. familiar, and (3) Productivity: productive vs. receptive. We assumed that the activities that are categorized as more active, novel, and productive could be considered as a cognitive reserve proxy., Methods: To test this hypothesis, a sample of 237 participants older than 50 years (M age  = 58.76 ± 6.66; 63.7% women) was recruited to take part in the study. Episodic, semantic and working memory were assessed with computerized battery tests (Sepidar) and a self-report questionnaire was used to assess intellectual activities. Activities were categorized in terms of; (1) passive, familiar, and receptive activities (radio/watching TV), (2) active, familiar, and receptive activities (solving crosswords), (3) active, novel, and receptive activities (reading), and (4) active, novel, and productive activities (writing)., Results: The results indicated that writing moderates the effect of age on episodic and semantic memory. Reading only moderates the effect of age on semantic memory, and radio/watching TV and solving crosswords do not play a role in moderation analysis., Conclusions: Our finding suggests that intellectual activities have different moderating effects on the relationships between age and memory performance. Individuals with high levels of participation in novel and productive activities over the life course are less likely to clinically demonstrate cognitive impairments. Our results support the potential benefit of the three-dimensional model to provide a better insight into the complex role of intellectual activities in cognitive reserve, particularly for older adults. Further research is needed to evaluate the efficacy and the benefits of the model., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cognitive reserve has shown promise as a justification for neuropathologically unexplainable clinical outcomes in Alzheimer's disease. Recent evidence suggests this effect may be replicated in conditions like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. However, the relationships between cognitive reserve and different cognitive abilities, as well as motor outcomes, are still poorly understood in these conditions. Additionally, it is unclear whether the reported effects are confounded by medication. This review analysed studies investigating the relationship between cognitive reserve and clinical outcomes in these α-synucleinopathy cohorts, identified from MEDLINE, Scopus, psycINFO, CINAHL, and Web of Science. 85 records, containing 176 cognition and 31 motor function effect sizes, were pooled using multilevel meta-analysis. There was a significant, positive association between higher cognitive reserve and both better cognition and motor function. Cognition effect sizes differed by disease subtype, cognitive reserve measure, and outcome type; however, no moderators significantly impacted motor function. Review findings highlight the clinical implications of cognitive reserve and importance of engaging in reserve-building behaviours., Competing Interests: Declaration of Competing Interest The authors declare no competing interests and have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: This review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR., Methods: We revised the literature in the context of CR. A total of 842 articles were identified, then we rigorously assessed the relevance of articles based on titles and abstracts, employing a systematic approach to eliminate studies that did not align with our research objectives., Results: We evaluate-also in a critical way-the methods commonly used to define and measure CR, including sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures. The challenges and limitations of these measures are discussed, emphasizing the need for more targeted research to improve the understanding, definition, and measurement of CR., Conclusions: The review underscores the significance of comprehending CR in the context of both normal and pathological brain aging and emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation in both healthy and neurologically impaired older individuals., Highlights: This review examines the concept of cognitive reserve in brain aging, in the context of dementia and its early stages. We have evaluated the methods commonly used to define and measure cognitive reserve. Sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures are discussed. The review emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: While evidence supports cognitive reserve (CR) in preserving cognitive function, longitudinal validation of CR proxies, including later-life factors, remains scarce. This study aims to validate CR's stability over time and its relation to cognitive function in rural Chinese older adults., Methods: Within the project on the health status of rural older adults (HSRO), the survey included baseline assessment (2019) and follow-up assessment (2022). 792 older adults (mean age: 70.23 years) were followed up. The confirmatory factor analysis (CFA) was constructed using cognitive reserve proxies that included years of formal education, social support, hobbies, and exercise. We examined the longitudinal validity of the CR factor using confirmatory factor analyses and measurement invariance and explored the association of CR with cognition using Spearman's correlation and Generalized Estimating Equations (GEE)., Results: The results showed that CR's CFA structure was stable over time (T0, χ 2 /df: 3.21/2; RMSEA: 0.02, and T1, χ 2 /df: 7.47/2; RMSEA: 0.05) and that it accepted both configural and metric invariance (Δχ 2 /df = 2.28/3, P = 0.52). In addition, it was found that CR had a stable positive relationship with cognitive function across time (T0, r = 0.54; T1, r = 0.49). Furthermore, longitudinal CR were associated with MMSE (β = 2.25; 95%CI = 2.01 ~ 2.49)., Conclusions: This study provided valuable evidence on the stability and validity of cognitive reserve proxy measures in rural Chinese older adults. Our findings suggested that cognitive reserve is associated with cognitive function over time and highlighted the importance of accumulating cognitive reserve in later life., (© 2024. The Author(s).)